反应详情

To a cooled solution (0° C.) under nitrogen of trans-4-(butoxycarbonyl)cyclohexanecarboxylic-acid (18.9 g, 83 mmol) in CH2Cl2 (150 mL) was added a catalytic amount of DMF (30 μL) followed by oxalyl chloride (7.97 mL, 91 mmol). The reaction mixture was then allowed to slowly warm to room temperature where it was stirred for 14 hours at which point it was concentrated to a yellow oil and dried under vacuum for 3 hours. The residue (consisting primarily of butyl trans-4-(chlorocarbonyl)cyclohexanecarboxylate) was diluted with THF (200 mL) and cooled in an ice bath. To this solution was added PdCl2(dppf)-CH2Cl2 (3.38 g, 4.14 mmol, 5 mol %) followed by dimethyl zinc (2 M in PhCH3, 29 mL, 58 mmol, 0.7 equiv) at such a rate that the internal temperature did not exceed 15° C. The cooling bath was then removed and after 2 hours of stirring at room temperature the reaction mixture was re-cooled to 0° C. where it was diluted carefully with H2O. After the initial exotherm had subsided, sufficient 1N HCl and EtOAc were introduced such that a homogenous biphasic mixture formed. The layers were separated, the organic washed a second time with H2O then dried with MgSO4, filtered and concentrated in vacuo. The crude residue was absorbed on silica and purified by flash chromatography to afford butyl trans-4-acetylcyclohexanecarboxylate as a non-viscous orange oil. MS ESI calcd. for C13H23O3 [M+H]+ 227. found 227. 1H NMR (500 MHz, CDCl3) δ 4.06 (t, J=6.6 Hz, 2H), 2.33 (m, J=3.4, 11.8 Hz, 1H), 2.24 (tt, J=3.6, 12.1 Hz, 1H), 2.14 (s, 3H), 2.11-2.02 (m, 2H), 1.99 (d, J=13.8 Hz, 2H), 1.66-1.55 (m, 2H), 1.51-1.40 (m, 2H), 1.39-1.29 (m, 4H), 0.93 (t, J=7.4 Hz, 3H).

1. concentrationwas concentrated to a yellow oil
2. customdried under vacuum for 3 hours
3. additionwas diluted with THF (200 mL)
4. temperaturecooled in an ice bath
5. customdid not exceed 15° C
6. customThe cooling bath was then removed and after 2 hours
7. stirringof stirring at room temperature the reaction mixture
8. temperaturewas re-cooled to 0° C. where it
9. additionwas diluted carefully with H2O
10. additionsufficient 1N HCl and EtOAc were introduced such that a homogenous biphasic mixture
11. customformed
12. customThe layers were separated
13. washthe organic washed a second time with H2O
14. dry with materialthen dried with MgSO4
15. filtrationfiltered
16. concentrationconcentrated in vacuo
17. customThe crude residue was absorbed on silica
18. custompurified by flash chromatography